Brain Structural Networks in Mouse Exposed to Chronic Maternal Undernutrition

Abstract

Brain structural connectivity is known to be altered in cases of intrauterine growth restriction and premature birth, although the specific effect of maternal nutritional restriction, a common burden in human populations, has not been assessed yet. Here we analyze the effects of maternal undernutrition during pregnancy and lactation by establishing three experimental groups of female mice divided according to their diet: control (Co), moderate calorie-protein restriction (MCP) and severe protein restriction (SP). Nutritionally restricted dams gained relatively less weight during pregnancy and the body weight of the offspring was also affected by maternal undernutrition, showing global growth restriction. We performed magnetic resonance imaging (MRI) of the offspring's brains after weaning and analyzed their connectivity patterns using complex graph theory. In general, changes observed in the MCP group were more subtle than in SP. Results indicated that brain structures were not homogeneously affected by early nutritional stress. In particular, the growth of central brain regions, such as the temporo-parietal cortex, and long integrative myelinated tracts were relatively preserved, while the frequency of short tracts was relatively reduced. We also found a differential effect on network parameters: network degree, clustering, characteristic path length and small-worldness remained mainly unchanged, while the rich-club index was lower in nutritionally restricted animals. Rich-club decrease reflects an impairment in the structure by which brain regions with large number of connections tend to be more densely linked among themselves. Overall, the findings presented here support the hypothesis that chronic nutritional stress produces long-term changes in brain structural connectivity.

Understanding the Links among Maternal Diet, Myelination, and Depression: Preclinical and Clinical Overview

“…Interestingly, chronic nutritional stress using a low-calorie protein diet in mothers during pregnancy and lactation produced long-term changes in network parameters in offspring brain [116] and in the optic nerve [117]; however, this altered diet did not change the long integrative myelinated tracks in mice pups, but it reduced the frequency of short tracks in the central brain regions [116]. The rats fed an iodine-deficient diet from 3 months before pregnancy to the end of lactation altered the hippocampal myelin at PND 14 and 21, whereas hypothyroxinemia reduced the expression of Olig2 and myelin-related proteins in these rats, suggesting that impairment of hippocampal myelinated growth may cause the neurological deficits and alterations of brain function in offspring [118].…”

Morphological correspondence between brain and endocranial surfaces in mice exposed to undernutrition during development

“…All procedures were executed following the guidelines of the Canada Council on Animal Care (UCalgary) and with the approval of the Committee for the Care and Use of Experimental Animals (CICUAL) of the Faculty of Veterinary of the National University of La Plata (Protocol number 42-2-14P). More details on the experimental design and procedures are available at Barbeito-Andrés et al (2018).…”

“…We analyzed 21 specimens of both sexes from at least three different dams by experimental group (Co = five males and three females, LCP = three males and three females, and LP = three males and four females). Males and females were pooled given that we previously reported no significant differences between sexes on body and gross brain size (Barbeito-Andrés et al, 2018). It is worth noting that Co group had a significantly larger body weight compared to the other groups (Barbeito-Andrés et al, 2018).…”

“…Males and females were pooled given that we previously reported no significant differences between sexes on body and gross brain size (Barbeito-Andrés et al, 2018). It is worth noting that Co group had a significantly larger body weight compared to the other groups (Barbeito-Andrés et al, 2018).…”

Lack of head sparing following third-trimester caloric restriction among Tanzanian Maasai

“…This phenomenon, termed brain-sparing, is a common feature of growth-restricted neonates in both humans and in rodent models, and it is thought to reflect selection to mitigate the high functional cost of reduced brain growth and compromised neural development [ 30 ]. However, several experimental and population studies show that early exposure to calorie and protein restriction, even when it is moderate, affects the cellular composition, brain connectivity, and growth of brain components, which can persist long after conditions are improved [ 31 , 32 ]. Fetal growth restriction may not only be associated with increased risk of morbidity and mortality, but also with undernutrition-related cognitive impairment and neurological disorders [ 33 – 35 ].…”